A Two-arm, Non-randomised, Prospective, Multicentre Study Using Magnetic Resonance Imaging (MRI) Findings and Pathology Features to Select Patients With Early Breast Cancer for Omission of Post-operative Radiotherapy
Overview
- Phase
- N/A
- Intervention
- Arm A: Radiotherapy Omission
- Conditions
- Breast Cancer
- Sponsor
- Breast Cancer Trials, Australia and New Zealand
- Enrollment
- 1400
- Locations
- 15
- Primary Endpoint
- Ipsilateral Invasive Recurrence Rate (IIRR) in low-risk patients omitting RT at a median of 5 years follow up
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
The PROSPECTIVE trial aims to find out if using the results of Magnetic Resonance Imaging (MRI) for early breast cancer can select people to not have radiotherapy and still have a low chance of the cancer coming back after surgery.
The main question it aims to answer is:
* Will cancer come back in the same breast as the original cancer in patients who have surgery for their breast cancer, but who don't have radiotherapy afterwards because the results of an MRI before surgery showed favourable characteristics for not having radiotherapy.
Detailed Description
Breast cancer is the most common serious malignancy in women and most patients are suitable for therapy involving surgery and adjuvant radiotherapy (RT). For most patients, there is a lack of evidence that breast conserving surgery without adjuvant RT is safe and therefore patients bear the costs, inconvenience and morbidity of RT. Prior attempts to identify large subsets of patients for whom RT can be safely omitted based on clinicopathological features of the index cancer have had limited success, and so RT is currently omitted only in some women over 65 or 70 with small low risk cancers. Identification of a much larger subset of patients in whom adjuvant RT could be safely omitted would be hugely significant, not only to the patients, but to the entire health system. The ANZ 1002 PROSPECT study was a two-arm phase II study that used breast MRI findings and pathological features to identify a group of patients with low risk early breast cancer in whom RT may be safely omitted. The findings at the primary strongly support the hypothesis and suggest that the combination of preoperative MRI and pathological features can identify a substantial group of early breast cancer patients in whom adjuvant RT can be safely omitted. A Health Economic analysis of PROSPECT found that the avoided costs of RT and its potential side effects is likely to substantially outweigh the extra cost of MRI scans and associated investigations. Parallel cross-sectional studies assessing Fear of Cancer Recurrence (FCR) and Health Related Quality of Life (HRQoL) in patients taking part in PROSPECT who either did or did not receive RT and a control group found a substantially lower FCR in PROSPECT patients who omitted RT as well as improved HRQoL. The majority of screened and eligible patients (427/443 and 193/201, respectively) for PROSPECT were recruited from two Australian sites. Before the PROSPECT approach can be widely adopted, the findings need to be replicated in a multicentre, international study. In addition, patient reported outcomes and health economic assessments need to be performed prospectively and longitudinally. PROSPECTIVE is the follow-up to PROSPECT which will address these issues, and also include translational research aspects to further study the natural history and outcomes of this group of lower risk early breast cancers.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For inclusion in the study at Registration, participants must fulfil all of the following criteria:
- •Has provided written, informed consent to participate in the study.
- •Female participants ≥ 50 years old with histologically\* confirmed ER-positive and/or HER2-positive invasive breast cancer.
- •Has a life expectancy of at least 10 years and suitable for prolonged follow up for 10 years.
- •Breast imaging indicating unifocal, unilateral breast cancer must have been performed before pre-registration.
- •Willing/able to have surgery within 8 weeks of registration or pre-operative MRI, whichever occurs later.
- •Have ECOG performance status 0-
- •Oestrogen receptor and progesterone receptor status of invasive cancer will be assessed by immunohistochemistry on the diagnostic core biopsy specimen. The IHC results will be reported as percentage of nuclei stained and a score of intensity from negative, weak, intermediate or high staining
- •HER2 neu status will be assessed by immunohistochemistry and will be scored as follows46:
- •0 or 1+ (HER2 negative): No staining or membrane staining that is incomplete and is faint/barely perceptible and in ≤ 10% of tumour cells (0); or incomplete membrane staining that is faint/barely perceptible and in \> 10% of tumour cells (1+).
Exclusion Criteria
- •Any one of the following at Registration is regarded as a criterion for exclusion from the study:
- •Triple negative breast cancer (ER-negative and PR-negative and HER2-negative) where ER and PR positivity is defined as ≥ 10% staining on IHC.
- •Previous invasive breast cancer and/or DCIS in either breast.
- •Prior RT to the breast or chest.
- •Participants who plan to have a mastectomy for the index cancer.
- •Lymphovascular invasion (LVI) reported on diagnostic core biopsy.
- •Multifocal/multicentric breast cancer on breast imaging before registration.
- •Distant metastasis at diagnosis.
- •Bilateral breast cancer
- •Known breast cancer predisposition gene mutation carriers (BRCA1, BRCA2, PALB2, CHEK2, ATM, CDK1, p53, BARD1, RAD51C, RAD51D, CDH1, STK11, PTEN).
Arms & Interventions
Radiotherapy Omission
Participants with nil, minimal or mild parenchymal enhancement on pre-operative MRI whose pathology meets inclusion/exclusion requirements for omission of post-operative radiotherapy will be allocated to Arm A, unless the participant prefers to receive Standard Treatment (Arm B) or following clinical team recommendation. Arm A participants will be divided into 2 groups: * Arm A1: Grade 1 or 2/HER2 negative ("low risk") * Arm A2: Grade 3 and/or HER2 positive ("high risk")
Intervention: Arm A: Radiotherapy Omission
Standard Treatment
Participants who are found to be ineligible for RT omission on study; includes management of MRI-detected lesions. Participants with any of: * Moderate or marked parenchymal enhancement on pre-operative MRI * A malignant occult lesion identified on MRI; or * Pathology that does not meet inclusion/exclusion criteria will receive standard multidisciplinary team recommendations to guide treatment. Participants may also be included in Arm B due to their own preference or following clinical team recommendation.
Intervention: Arm B: Standard Treatment
Outcomes
Primary Outcomes
Ipsilateral Invasive Recurrence Rate (IIRR) in low-risk patients omitting RT at a median of 5 years follow up
Time Frame: Median of 5 years follow up (when 300th low risk patient in Arm A reaches 5 years follow up)
To determine the ipsilateral invasive recurrence rate (IIRR) in lower risk patients with unequivocally unifocal breast cancer and on breast MRI and favourable clinico-pathological features.
Secondary Outcomes
- PRO: Levels of FCR and perception of risk of recurrence in Arm A over time.(At median of 24 months post-surgery)
- PRO: Quality of Life Years (QALYs) between Arms A and Arm B.(At a median of 24 months follow up post-surgery.)
- PRO: Difference in QALYs over time between Arm A and Arm B.(From registration to allocation, 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery..)
- PRO: Difference in Decision Regret between Arm A and Arm B.(At median of 24 months follow up post-surgery.)
- PRO: Decision Regret in Arm A.(At median 24 months of follow-up post-surgery.)
- PRO: Overall mental health and depression over time between Arm A and Arm B.(From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.)
- PRO: Overall mental health and differences over time in anxiety in Arm A.(At 24 months median follow-up post-surgery.)
- PRO: Overall mental health (depression) over time between Arm A and Arm B.(From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.)
- PRO: Overall mental health (anxiety) over time between Arm A and Arm B.(From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.)
- Ipsilateral Invasive Recurrence Rate (IIRR) in all participants omitting RT at a median of 10 years follow up after surgery.(Median of 10 years follow up after surgery.)
- IIRR in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.(Median of 5 years and 10 years follow up after surgery.)
- Ipsilateral DCIS recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.(Median of 5 and 10 years follow up after surgery.)
- The combined ipsilateral DCIS and invasive recurrence rate (IRR) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.(Median of 5 and 10 years follow up after surgery.)
- Distant recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B..(Median of 5 and 10 years follow up after surgery.)
- Regional recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.(Median of 5 and 10 years follow up after surgery.)
- Contralateral DCIS and invasive breast cancer rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B(Median of 5 and 10 years follow up after surgery.)
- PRO: Health Related Quality of Life (HRQoL) (functional and aesthetic outcomes, fatigue, body image, financial toxicity) in Arm A(From allocation to 3-, 6-, 12-, 24- and 60 months median follow up post-surgery)
- PRO: Difference over time in HRQoL (functional and aesthetic outcomes, fatigue, body image, financial toxicity) between Arm A and Arm B.(From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.)
- Breast cancer specific survival (BCSS) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B(Median of 5 and 10 years follow up after surgery.)
- PRO: Difference in FCR and perception of risk of recurrence between Arm A and Arm B.(From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.)
- PRO: Perception of risk of recurrence in Arm A and between Arm A and Arm B.(From allocation to 3-, 6-, 12-, 24- and 60 months median follow up post-surgery)
- PRO: Health Related Quality of Life (HRQoL) (functional and aesthetic outcomes, fatigue, body image, financial toxicity) between Arm A and Arm B.(At a median of 24 months post-surgery.)
- Overall Survival (OS) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.(Median of 5 and 10 years follow up after surgery.)
- PRO: Fear of Cancer Recurrence(Median 24 months post-surgery)